Organic electronics for high-resolution electrocorticography of the human brain

Abstract

Localizing neuronal patterns that generate pathological brain signals may assist with tissue resection and intervention strategies in patients with neurological diseases. Precise localization requires high spatiotemporal recording from populations of neurons while minimizing invasiveness and adverse events. We describe a large-scale, high-density, organic material-based, conformable neural interface device ("NeuroGrid") capable of simultaneously recording local field potentials (LFPs) and action potentials from the cortical surface. We demonstrate the feasibility and safety of intraoperative recording with NeuroGrids in anesthetized and awake subjects. Highly localized and propagating physiological and pathological LFP patterns were recorded, and correlated neural firing provided evidence about their local generation. Application of NeuroGrids to brain disorders, such as epilepsy, may improve diagnostic precision and therapeutic outcomes while reducing complications associated with invasive electrodes conventionally used to acquire high-resolution and spiking data.

Keywords: NeuroGrid; Organic electronics; conducting polymers; epilepsy; human electrocorticography.

Fig. 1. NeuroGrid structure and characterization for intraoperative recording in human subjects.

(A) Photomicrograph of 240-channel NeuroGrid. Scale bar, 1 mm. (B) Magnified microscopy image of 10-μm² electrodes arranged in 2 x 2 tetrodes, with 2-mm spacing between each tetrode. Physical perforations between electrode groups are also visible (yellow circle). Scale bar, 1 mm. (C) High-density patterning of conducting polymer–coated electrodes (10-μm² surface area, 23-μm interelectrode spacing) comprising a single tetrode. Scale bar, 20 μm. (D) Histogram demonstrating impedance of 240 electrodes comprising a single NeuroGrid; yield = 87.5% (210 of 240 electrodes with impedance magnitude between 10 and 100 kilohm). Inset: representative electrochemical impedance magnitude and phase of a single electrode across the range of physiological frequencies. (E) Intraoperative photograph showing 240-channel NeuroGrid (yellow circle) conforming to the surface of the cortex with accompanying headstage. Scale bar, 1 cm.

Fig. 2. Intraoperative NeuroGrid recordings reveal brain state dynamics in anesthetized and awake human subjects.

(A) Raw LFP trace (top) and corresponding low- (middle) and high-frequency (bottom) spectrograms from a subject under propofol anesthesia using a 120-electrode NeuroGrid; corresponding power spectrum shown as an inset. Scale bar, 500 ms, 200 μV. a.u., arbitrary units. (B) Subject under low-concentration sevoflurane anesthesia using a 240-electrode NeuroGrid; conventions as in (A). Scale bar, 500 ms, 200 μV. (C) NeuroGrid recording from awake subject participating in language mapping tasks using a 120-electrode NeuroGrid; conventions as in (A). Scale bar, 1 s, 500 μV. (D) Clinical ECoG recording from awake subject in (C) participating in language mapping tasks; conventions as in (A). Scale bar, 1 s, 500 μV.

Fig. 3. Spatial distribution of localized LFP and neural spiking activity across the NeuroGrid.

(A) Raw LFP traces (left) from multiple recording electrodes of the NeuroGrid in a subject under general anesthesia using a 120-electrode NeuroGrid demonstrating localized β frequency oscillation (blue) and δ wave (green). Scale bar, 500 ms, 200 μV. Corresponding colormap of power in β frequency band across 8 × 15 array. (B) Raw LFP traces (left) from electrodes across the NeuroGrid in an awake subject using a 120-electrode NeuroGrid reveal localized distribution of IED waveform. Scale bar, 0.5 s, 1 mV. Corresponding colormap of latency to maximal negativity of IED waveform; * denotes reference electrode for latency measurement; electrodes that do not exhibit an IED waveform are in dark blue. (C) High-pass–filtered traces (250 Hz) from subject in (B) during the listening phase of a language task (left) and from subject under anesthesia using a 240-electrode NeuroGrid (right). Red dashed line shows 3× noise floor; red circles are peaks of detected action potentials. Scale bar, 25 ms, 60 μV. (D) Examples of the spatial extent of extracellular action potentials over the geometry of the array by spike-triggered averaging during the detected spike times from subject in (B). Scale bar, 1.5 ms, 50 μV. (E) Average normalized neural firing rate recorded from representative electrode during δ wave (average waveform overlaid in black) from subject under sevoflurane anesthesia using 240-electrode NeuroGrid. (F) Polar plot showing phase-locking of sample neural firing to β frequency oscillations recorded from representative electrode during sevoflurane anesthesia using a 120-electrode NeuroGrid. (G) Sample average normalized neural firing rate during time window of IED occurrence in awake subject. Black trace (top) is average IED waveform, with dashed line denoting time of the local peak negativity of the IED waveform.

Fig. 4. Coherence of neural activity patterns at millimeter and micrometer scales in anesthetized and awake human subjects.

(A) Coherence between recording electrodes spaced over millimeters at each frequency band in the awake subject using 120-electrode NeuroGrid. Coherence values for pairs of electrodes were averaged in bins of 2 mm and plotted as means ± SEM. (B) Coherence between recording electrodes spaced over millimeters at each frequency band in an anesthetized subject using 120-electrode NeuroGrid. Conventions as in (A). (C) Coherence between recording electrodes spaced over hundreds of micrometers at each frequency band in an anesthetized subject using 64-electrode NeuroGrids. Coherence values for pairs of electrodes were averaged in bins of 100 μm and plotted as means ± SEM. Color conventions as in (A).